Impact of CYP2C92* and *3 polymorphisms on valproate-associated adverse drug reactions in individuals living with epilepsy: a case-control study.

Personalized medicine Pub Date : 2023-09-01 Epub Date: 2023-10-09 DOI:10.2217/pme-2023-0033

Kirubakaran Ramakrishnan, Ramasamy Kesavan, Shravan Venkatraman, Sunil K Narayan, Ramachandran Ramesh Kumar, Deepak Shewade

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Abstract

Epilepsy is characterized by repeated seizure activity. Valproate, a commonly used antiepileptic drug, shows large inter-individual variation in plasma valproic levels and causes many adverse drug reactions. Aim: To find the influence of CYP2C9*2 and *3 polymorphisms on valproate-associated adverse drug reactions and plasma valproic acid levels in people with epilepsy. Methods: We recruited 158 people with epilepsy (79 cases and 79 controls) from an epilepsy clinic. Steady-state plasma valproic acid levels were measured using liquid chromatography-mass spectrometry and genotyping of CYP2C9 variants was carried out with helps of RT-PCR. Results: The presence of a mutant heterozygous genotype showed an odds ratio (OR) of 2.82 (95% CI: 1.10-7.24) and the adjusted OR was 5.39 (95% CI: 1.69-17.16). There was no significant difference in steady-state plasma valproate concentration between genotypes. Conclusion: The presence of a mutant heterozygous CYP2C9 genotype possesses five-times the risk of developing adverse drug reactions to valproate in people with epilepsy.

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CYP2C9*2和*3多态性对癫痫患者丙戊酸钠相关药物不良反应的影响：一项病例对照研究。

癫痫的特点是反复发作。丙戊酸钠是一种常用的抗癫痫药物，其血浆丙戊酸水平存在较大的个体间差异，并导致许多药物不良反应。目的：探讨CYP2C9*2和*3多态性对癫痫患者丙戊酸相关药物不良反应和血浆丙戊酸水平的影响。方法：我们从一家癫痫诊所招募了158名癫痫患者（79例和79名对照）。使用液相色谱-质谱法测量稳态血浆丙戊酸水平，并借助RT-PCR进行CYP2C9变体的基因分型。结果：突变杂合基因型的存在显示优势比（OR）为2.82（95%CI:1.10-7.24），调整后的OR为5.39（95%CI:1.69-17.16）。结论：突变杂合CYP2C9基因型的存在使癫痫患者对丙戊酸钠产生不良药物反应的风险增加5倍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Personalized medicine

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